Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution. First, the tibial axis in a CT scan was aligned with the FE loading axis. FE cubic mesh elements were modeled using image voxels, and CT intensity values were calibrated to ash density defining mechanical properties at individual elements. For FEA of an upright volume of interest (VOI), the bottom surface was fixed, and a constant displacement was applied at each vertex on the top surface simulating different loading conditions. The method was implemented and optimized using the ANSYS software. CT-derived computational modulus values were repeat scan reproducible (intraclass correlation coefficient [ICC] ≥ 0.97) and highly correlated (r ≥ 0.86) with the micro-CT (µCT)-derived values. FEA-derived von Mises stresses over the segmented Tb microregion were significantly higher (p < 1 × 10-11) than that over the marrow space. In vivo results showed that both shear and compressive modulus for males were higher (p < 0.01) than for females. Effect sizes for different modulus measures between males and females were moderate-to-high (≥0.55) and reduced to small-to-negligible (<0.40) when adjusted for pure lean mass. Among body size and composition attributes, pure lean mass and height showed highest (r ∈ [0.45 0.56]) and lowest (r ∈ [0.25 0.39]) linear correlation, respectively, with FE-derived modulus measures. In summary, CT-based nonlinear FEA provides an effective surrogate measure of Tb microstructural stiffness, and the relaxation of binary segmentation will extend the scope for FEA in human studies using in vivo imaging at relatively low-resolution. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Interscholastic Athletics and Bone Strength: The Iowa Bone Development Study.

ABSTRACT: Pashkova, A, Hartman, JM, Letuchy, EM, and Janz, KF. Interscholastic athletics and bone strength: the Iowa bone development study. J Strength Cond Res 36(5): 1271-1276, 2022-The objective of this study was to determine the relationship between adolescents' participation in various interscholastic sports and differences in bone strength outcomes. Subjects (N = 380) were recruited from the Iowa Bone Development Study and categorized based on sport participation into 3 power groups: no-power, low-power, and high-power. Sports such as basketball, cheerleading/poms, gymnastics, volleyball, track, football, tennis, and soccer were considered high-power. Peripheral quantitative computed tomography (pQCT) was used to determine bone measures of polar stress-strain index (measure of torsion strength), cortical content (measure of cortical bone size and area at the 66% tibia site), and bone strength index (measure of compression strength based on total bone density and area at the 4% tibia site). Adjusted pairwise comparison for group least squares means high-power sport participation compared with no-power sport participation showed significant differences in all bone strength outcomes for both men and women (p value < 0.01). There was a significant difference in all bone strength measures between low-power and no-power groups for men (p value < 0.05), but not women. Because of decreasing levels of physical activity in late adolescence, the promotion of high-power sports may be particularly important for optimal bone development in the final years before peak bone mass.

Quantitative CT-Based Methods for Bone Microstructural Measures and Their Relationships With Vertebral Fractures in a Pilot Study on Smokers.

Osteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT-based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra-high-resolution (UHR) CT and micro-CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5-year follow-up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT-derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro-CT-derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility-intra-class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non-fracture and fracture groups. Vertebral fracture-group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures-81.8% versus 63.2% for former smokers-the difference was not statistically significant. This pilot cross-sectional human study demonstrates CT-based peripheral bone microstructural differences among smokers with and without vertebral fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Youth Sports Participation Is More Important among Females than Males for Predicting Physical Activity in Early Adulthood: Iowa Bone Development Study.

A gender difference in youth sports and physical activity participation is well documented. However, research is limited to understand potential gender difference in the long-term effects of youth sports participation. The study aim was to compare the likelihood of meeting the aerobic Physical Activity Guidelines (PAG) in early adulthood by youth sports participation patterns among females and males. The study sample included 582 Iowa Bone Development Study participants (Iowa, USA). Participation in organized sports was assessed using a physical activity questionnaire 19 times on average between age 6 and 17 years. Accelerometer and dual-energy X-ray absorptiometry assessments were conducted at an average age of 23 years. Group-based trajectory analysis was conducted to identify youth sports participation trajectory patterns. Multivariable logistic regression analysis was conducted to examine the association between youth sports participation patterns and meeting the PAG in adulthood. We identified three youth sports participation patterns: "continuous participation," "drop-out," and "no participation." Females in the continuous participation group were more likely to meet the aerobic PAG at age 23 years, compared to females in the no-participation group (OR = 2.63; 95% CI = 1.05, 6.55) or the drop-out group (OR = 2.55; 95% CI = 1.38, 4.69). However, among males, youth sports participation patterns were not significantly associated with meeting the aerobic PAG at age 23 years. In conclusion, this study suggests that youth sports participation could be more important among females than males for predicting physical activity in early adulthood.

Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT).

PURPOSE: The aim of this study was to examine the effects of period-specific and cumulative fluoride (F) intake on bone at the levels of cortical and trabecular bone microstructural outcomes at early adulthood using emerging multi-row detector computed tomography (MDCT)-based novel techniques. METHODS: Ultra-high resolution MDCT distal tibia scans were collected at age 19 visits under the Iowa Bone Development Study (IBDS), and cortical and trabecular bone microstructural outcomes were computed at the distal tibia using previously validated methods. CT scans of a tissue characterization phantom were used to calibrate CT numbers (Hounsfield units) into bone mineral density (mg/cc). Period-specific and cumulative F intakes from birth up to the age of 19 years were assessed for IBDS participants through questionnaire, and their relationships with MDCT-derived bone microstructural outcomes were examined using bivariable and multivariable analyses, adjusting for height, weight, maturity offset (years since age of peak height velocity (PHV)), physical activity (questionnaire for adolescents (PAQ-A)), healthy eating index version 2010 (HEI-2010) scores, and calcium and protein intakes. RESULTS: MDCT distal tibia scans were acquired for 324 participants from among the total of 329 participants at age 19 visits. No motion artifacts were observed in any MDCT scans, and all images were successfully processed to measure cortical and trabecular bone microstructural outcomes. At early adulthood, males were observed to have stronger trabecular bone microstructural features, as well as thicker cortical bone (p < 0.01), as compared to age-similar females; however, females were found to have less cortical bone porosity as compared to males. Among participants with available F intake estimates (75 to 91% of the 324 with MDCT scans, depending on the period-specific F intake measure), no statistically significant associations were detected between any period-specific or cumulative F intake and bone microstructural outcomes of the tibia at the p < 0.01 level. Only for females, statistically suggestive associations (p < 0.05) were found between recent F intake (from 14 to 19 years) and trabecular mean plate width and trabecular thickness at the tibia. Those associations became somewhat weaker, but still statistically suggestive, for trabecular thickness in fully adjusted analysis with height, weight, PHV, calcium and protein intake, and HEI-2010 and PAQ-A scores as covariates. CONCLUSION: The findings show that the effects of lifelong or period-specific F intake from combined sources for adolescents typical to the United States Midwest region are not strongly associated with bone microstructural outcomes at age 19 years. These findings are generally consistent with previously reported results of IBDS analyses, which further confirms that effects of lifelong or period-specific F intake on skeletons in early adulthood are absent or weak, even at the levels of cortical and trabecular bone microstructural details.

Moderate-to-vigorous intensity physical activity trajectories during adolescence and young adulthood predict adiposity in young adulthood: The Iowa Bone Development Study.

This study examined the associations of moderate-to-vigorous intensity physical activity (MVPA) trajectories in adolescence through young adulthood with adiposity in young adults. Participants from The Iowa Bone Development Study cohort were longitudinally assessed (N = 297; 57% female). Accelerometry-measured MVPA (min/day) at ages 15 through 23 years, and fat mass and visceral adipose tissue mass indices (kg/m2, g/m2) derived from dual-energy X-ray absorptiometry scans at age 23 years were analyzed. Latent trajectory analyses classified MVPA into two patterns. Multivariable linear regression analyses showed that being in the high MVPA trajectory group was associated with lower fat mass index z-scores. Individuals who were consistently active with high MVPA (vs. moderately active with decreasing MVPA) during adolescence up until early young adulthood had less accumulation of total body adiposity in young adulthood. This study suggests that adopting a consistently active lifestyle throughout adolescence can result in healthier body composition in young adulthood.

CT-Based Characterization of Transverse and Longitudinal Trabeculae and Its Applications.

Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. Although, BMD is clinically used to define osteoporosis, there are compelling evidences that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount clinical significance. Tb consists of transverse and longitudinal micro-structures, and there is a hypothesis that transverse trabeculae improve bone strength by arresting buckling of longitudinal trabeculae. In this paper, we present an emerging clinical CT-based new method for characterizing transverse and longitudinal trabeculae, validate the method, and examine its application in human studies. Specifically, we examine repeat CT scan reproducibility, and evaluate the relationships of these measures with gender and body size using human CT data from the Iowa Bone Development Study (IBDS) (n = 99; 49 female). Based on a cadaveric ankle study (n = 12), both transverse and longitudinal Tb measures are found reproducible (ICC > 0.94). It was observed in the IBDS human data that males have significantly higher trabecular bone measures than females for both inner (p < 0.05) and outer (p < 0.01) regions of interest (ROIs). For weight, Spearman correlations ranged 0.43-0.48 for inner ROI measures and 0.50-0.52 for outer ROI measures for females versus 0.30-0.34 and 0.23-0.25 for males. Correlation with height was lower (0.36-0.39), but still mostly significant for females. No association of trabecular measures with height was found for males.

An 8-Year Longitudinal Analysis of Physical Activity and Bone Strength From Adolescence to Emerging Adulthood: The Iowa Bone Development Study.

PURPOSE: Most pediatric physical activity and bone health research has focused on the period immediately around puberty; few have addressed bone structural strength outcomes. This study assessed the magnitude and consistency of the longitudinal relationships between device-measured vigorous-intensity physical activity (VPA) and structural bone strength outcomes across adolescence to emerging adulthood. METHODS: Participants with 3 to 5 bone scans between the age of 11 and 19 years were studied (N = 439, 220 females, 1838 records). Dual-energy X-ray absorptiometry scans of the hip (hip structural analysis) and peripheral quantitative computed tomography scans of the tibia were obtained. Outcomes included femoral neck section modulus, femoral neck cross-sectional area, tibial Bone Strength Index, and tibial torsion strength (polar Strength Strain Index). Sex-specific bone mixed growth models were developed using biological age (chronological age - age at peak height velocity) as the time variable, and height, weight, and device-measured VPA as time-varying covariates. Models also included the VPA-biological age interaction. RESULTS: Individual-centered VPA and the VPA-biological age interaction were significantly, positively associated (P < .05) with Bone Strength Index, polar Strength Strain Index, section modulus, and cross-sectional area in males and females, indicating accumulative effects of VPA throughout maturation and beyond. CONCLUSION: Bone remains responsive to the mechanical loading of physical activity throughout adolescence and into emerging adulthood. Attention should be placed on promoting bone-strengthening physical activity after the prepubertal years when adult exercise patterns are likely formed.

Upper extremity disability and quality of life after breast cancer treatment in the Greater Plains Collaborative clinical research network.

PURPOSE: Chronic upper extremity disability (UED) is common after breast cancer treatment but under-identified and under-treated. Although UED has been linked to quality of life (QoL), the role of UED as mediator between contemporary treatment practices and QoL has not been quantified. This investigation describes UED in a contemporary sample of breast cancer patients and examines its relationship with personal and treatment factors and QoL. METHODS: Eight hundred and thirty-three women diagnosed at eight medical institutions during 2013-2014 with microscopically confirmed ductal carcinoma in situ or invasive stage I-III breast cancer were surveyed an average of 22 months after diagnosis. UED was measured with a modified QuickDASH and QoL with the FACT-B. The questionnaire also collected treatments, sociodemographic information, comorbidity, body mass index, and a 3-item health literacy screener. RESULTS: Women who received post-mastectomy radiation and chemotherapy experienced significantly worse UED and QoL. Women who had lower income, lower health literacy and prior diabetes, arthritis or shoulder diagnoses had worse UED. Patients with worse UED reported significantly worse QoL. Income and health literacy were independently associated with QoL after adjustment for UED but treatment and prior conditions were not, indicating mediation by UED. UED mediated 52-79% of the effect of mastectomy-based treatments on QoL as compared with unilateral mastectomy without radiation. UED and QoL did not differ by type of axillary surgery or post-mastectomy reconstruction. CONCLUSIONS: A large portion of treatment effect on QoL is mediated by UED. Rehabilitation practices that prevent and alleviate UED are likely to improve QoL for breast cancer survivors.

Mediating Effect of Muscle on the Relationship of Physical Activity and Bone.

PURPOSE: This study analyzed prospective associations between distinct trajectories of objectively measured physical activity (PA) and late adolescent bone parameters and explored the mediating effects of lean soft tissue, a surrogate of muscle mass to associations. METHODS: Physical activity was measured by accelerometry starting at age 5 yr and continuing at 8, 11, 13, 15, and 17 yr in approximately 524 participants from the Iowa Bone Development Study. Sex-specific group-based trajectory modeling was used to construct developmental trajectories of moderate- and vigorous-intensity PA (MVPA) from childhood to late adolescence. At age 17 yr, proximal femur bone mineral density (aBMD) was assessed by dual X-ray energy absorptiometry, and its distribution was calculated by aBMD ratios. Specific geometric measures of the proximal femur were assessed using hip structural analysis. RESULTS: A significant portion of the total effect of MVPA from age 5 to 17 yr on bone parameters at age 17 yr was explained by an increase in leg lean soft tissue in both sexes. For males and females, indirect effects were observed on the total and all regional proximal femur aBMD, and on the ratio between the inferomedial and superolateral neck aBMD. The effect on the ratio between the trochanter and the total proximal femur was specific to females, whereas the effect on the hip axis length was specific to males. Direct effects of MVPA on aBMD were identified only in males. CONCLUSIONS: Using robust mediation analysis, this is the first study addressing the indirect effect (through muscle) of PA across childhood and adolescence on proximal femur bone parameters. To improve bone health at the proximal femur, the results suggest PA interventions during growth that increase muscle mass, particularly in females.

Contribution of High School Sport Participation to Young Adult Bone Strength.

INTRODUCTION: Nearly 8 million American adolescents participate in sports. Participation declines in young adulthood. PURPOSE: This study assessed longitudinal effects of high school sport participation and muscle power on young adult bone strength. METHODS: Two hundred twenty-eight young adults from the Iowa Bone Development Study completed an interscholastic sport participation questionnaire. Current physical activity (PA) behaviors were assessed via questionnaire. Dual x-ray absorptiometry assessed hip areal bone mineral density and was used with hip structure analysis to estimate femoral neck section modulus and hip cross-sectional area. Peripheral quantitative computed tomography provided strength-strain index and bone strength index at 38% and 4% midshaft tibial sites, respectively. Vertical jump estimated muscle power at 17 yr. Sex-specific multiple linear regression predicted young adult bone outcomes based on sport participation groups. Mediation analysis analyzed the effects of muscle power on relationships between sport participation and bone strength. RESULTS: At follow-up, males participating in any interscholastic sport had greater bone strength than males who did not participate in sport. The explained variability in bone outcomes was 2% to 16%. Females who participated in sports requiring muscle power had greater bone strength than females who did not participate in sports or females who participated in nonpower sports (explained variability was 4%-10%). Muscle power mediated 24.7% to 41% of the effect of sport participation on bone outcomes in males and 19.4% to 30% in females. CONCLUSIONS: Former male interscholastic sport participants and female interscholastic power sport participants have stronger bones than peers even when adjusting for current PA. Muscle power did not fully explain differences in all bone outcomes, suggesting that sport participation has additional bone health benefits.

Associations of fluoride intake with children's cortical bone mineral and strength measures at age 11.

OBJECTIVES: There is strong affinity between fluoride and calcium, and mineralized tissues. Investigations of fluoride and bone health during childhood and adolescence show inconsistent results. This analysis assessed associations between period-specific and cumulative fluoride intakes from birth to age 11, and age 11 cortical bone measures obtained using peripheral quantitative computed tomography (pQCT) of the radius and tibia (n = 424). METHODS: Participants were a cohort recruited from eight Iowa hospitals at birth. Fluoride intakes from water, other beverages, selected foods, dietary supplements, and dentifrice were recorded every 1.5-6 months using detailed questionnaires. Correlations between bone measures (cortical bone mineral content, density, area, and strength) and fluoride intake were determined in bivariate and multivariable analyses adjusting for Tanner stage, weight and height. RESULTS: The majority of associations were weak. For boys, only the positive associations between daily fluoride intakes for 0-3 years and radius and tibia bone mineral content were statistically significant. For girls, the negative correlations of recent daily fluoride intake per kg of body weight from 8.5 to 11 years with radius bone mineral content, area, and strength and tibia strength were statistically significant. No associations between cumulative daily fluoride intakes from birth to 11 years and bone measures were statistically significant. CONCLUSIONS: In this cohort of 11-year-old children, mostly living in optimally fluoridated areas, life-long fluoride intakes from combined sources were weakly associated with tibia and radius cortical pQCT measures.

Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: A prospective cohort study.

OBJECTIVE: To investigate the associations between period-specific and cumulative fluoride (F) intakes from birth to age 17 years, and radial and tibial bone measures obtained using peripheral quantitative computed tomography (pQCT). METHODS: Participants (n = 380) were recruited from hospitals at birth and continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone Development Study until age 17. Fluoride intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were determined every 1.5-6 months using detailed questionnaires. Associations between F intake and bone measures (cortical and trabecular bone mineral content [BMC], density and strength) were determined in bivariate and multivariable analyses adjusted for height, weight, maturity offset, physical activity, and daily calcium and protein intake using robust regression analysis. RESULTS: Fluoride intake ranged from 0.7 to 0.8 mg F/d for females and from 0.7 to 0.9 mg F/d for males. Spearman correlations between daily F intake and pQCT bone measures were weak. For females, Spearman correlations ranged from r = -.08 to .21, and for males, they ranged from r = -.03 to .30. In sex-specific, height-, weight- and maturity offset- partially adjusted regression analyses, associations between females' fluoride intake and bone characteristics were almost all negative; associations for males were mostly positive. In the fully adjusted models, which also included physical activity, and protein and calcium intakes, no significant associations were detected for females; significant positive associations were detected between F intake from 14 to 17 years and tibial cortical bone content (ß = 21.40, P < .01) and torsion strength (ß = 175.06, P < .01) for males. CONCLUSION: In this cohort of 17-year-old adolescents, mostly living in optimally fluoridated areas, lifelong F intake from combined sources was weakly associated with bone pQCT measures.

Where Are Antipsychotics Prescribed in Nursing Homes Initiated?

OBJECTIVES: To describe the settings of care in which antipsychotics that nursing home (NH) residents received were likely to have been initiated. DESIGN: Cross-sectional. SETTING: Iowa NHs. PARTICIPANTS: Fee-for-service Medicare beneficiaries who had NH stays between January 1, 2011, and December 31, 2014, and had new use of antipsychotics during their NH stays, defined as no antipsychotic use in NHs in the last 6 months. MEASUREMENTS: A linked dataset of Chronic Condition Data Warehouse Medicare claims and Long-Term Care Minimum Data Set (MDS) 3.0 was used to determine care settings of antipsychotic initiations. RESULTS: Of 7,496 residents with new antipsychotic use in NHs, 4,794 (64.0%, 95% confidence interval (CI) = 62.9-65.0%) initiated them in NHs, 1,392 (18.6%, 95% CI 17.7-19.5%) appeared to have had them initiated in hospitals, and 1,310 (17.5%, 95% CI = 16.6-18.3%) had antipsychotics first dispensed as outpatients. Antipsychotics were commonly prescribed during the early NH stays, and 3,026 (40.4%, 95% CI = 39.3-41.5%) of the entire sample received antipsychotic therapy within the first 7 days after NH admissions. Fifty-eight percent (n = 4,348) of the study residents initiating antipsychotics had potentially appropriate antipsychotic indications according toMDS records. CONCLUSION: Most residents initiated antipsychotic therapy in NHs, confirming that NH providers are appropriate primary target of interventions to reduce antipsychotic initiation in their residents. However, many antipsychotics were continued from other settings, indicating a need to evaluate the necessity of continued antipsychotic treatment after such transitions of care. J Am Geriatr Soc 66:1082-1088: 2018.

Does Visceral or Subcutaneous Fat Influence Peripheral Cortical Bone Strength During Adolescence? A Longitudinal Study.

This study evaluated the longitudinal relationships among visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and peripheral bone strength during adolescence. Fat and lean mass, VAT and SAT area, and android/gynoid (A/G) ratio were estimated with DXA. Our main outcome was strength-strain index (SSI), an indicator of peripheral bone strength estimated by pQCT at the radius and tibia. Sex-specific analyses evaluated the longitudinal bone-fat relationship from ages 11 to 19 years with linear mixed models using biological age as the time variable and adjusted for limb length and lean mass in 182 girls and 167 boys. Variables were standardized (mean = 0, SD = 1) prior to model fitting and results shown are parameter estimates ± SE. Fat mass and SAT were positively associated with SSI (radius: 0.07 ± 0.02, p = 0.003 and 0.05 ± 0.02, 0.041, respectively; tibia: 0.09 ± 0.02, p < 0.001 and 0.08 ± 0.02, p < 0.001, respectively) prior to, but not following adjustment for lean mass in girls. In contrast, fat mass and SAT were negatively associated with radial SSI, both before and after adjustment for lean mass in boys (fat mass: -0.05 ± 0.01, p = 0.001; SAT: -0.04 ± 0.01, p = 0.004). In full models, negative associations were limited to VAT in girls and included radial (-0.06 ± 0.02, p = 0.001) and tibial SSI (-0.04 ± 0.02, p = 0.033). For boys, there were no significant associations present between VAT and SSI at the radius or tibia. In analyses limited to obese participants, an A/G ratio was not significantly associated with SSI in girls, but was negatively associated with radial SSI regardless of adjustment for lean mass in boys (-0.06 ± 0.02, p = 0.018). These results that show a negative relationship between peripheral bone strength and VAT in girls, but greater total and central adiposity in boys, suggest these factors play a role in adequate acquisition of bone strength during adolescence. © 2017 American Society for Bone and Mineral Research.

Bipolar Disorder in Nursing Homes: Impact on Antipsychotic Use, Diagnosis Patterns, and New Diagnoses in People with Dementia.

OBJECTIVES: Nursing home quality measures include the proportion of residents who receive antipsychotics. Residents with bipolar disorder are included even though antipsychotics are FDA-approved for this indication. We evaluated how including residents with bipolar disorder impacted the antipsychotic use quality measure for long-stay residents. We evaluated the agreement of minimum data set (MDS) bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed before bipolar disorder, and how less-specific bipolar disorder diagnoses impacted findings. DESIGN: Cross-sectional study. SETTING: Nursing homes in Iowa. PARTICIPANTS: 21,955 long-stay nursing home residents in the first quarter of 2014. MEASUREMENTS: We identified antipsychotic use and bipolar disorder using MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We compared CCW condition onset dates to identify bipolar disorder diagnosed after dementia. RESULTS: The mean (SD) proportion receiving antipsychotics was 19.6% (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar disorder, unspecified" and "other bipolar disorders" diagnoses were excluded. Nearly three-quarters of residents with bipolar disorder had dementia. Over half of those with dementia had dementia first per CCW records. This proportion was lower among those with more specific bipolar disorder diagnoses or MDS bipolar disorder indicators. CONCLUSIONS: Bipolar disorder in nursing home residents is often first diagnosed after dementia using nonspecific diagnoses. This practice deserves further evaluation.

Quantitative imaging of peripheral trabecular bone microarchitecture using MDCT.

PURPOSE: Osteoporosis associated with reduced bone mineral density (BMD) and microarchitectural changes puts patients at an elevated risk of fracture. Modern multidetector row CT (MDCT) technology, producing high spatial resolution at increasingly lower dose radiation, is emerging as a viable modality for trabecular bone (Tb) imaging. Wide variation in CT scanners raises concerns of data uniformity in multisite and longitudinal studies. A comprehensive cadaveric study was performed to evaluate MDCT-derived Tb microarchitectural measures. A human pilot study was performed comparing continuity of Tb measures estimated from two MDCT scanners with significantly different image resolution features. METHOD: Micro-CT imaging of cadaveric ankle specimens (n=25) was used to examine the validity of MDCT-derived Tb microarchitectural measures. Repeat scan reproducibility of MDCT-based Tb measures and their ability to predict mechanical properties were examined. To assess multiscanner data continuity of Tb measures, the distal tibias of 20 volunteers (age:26.2±4.5Y,10F) were scanned using the Siemens SOMATOM Definition Flash and the higher resolution Siemens SOMATOM Force scanners with an average 45-day time gap between scans. The correlation of Tb measures derived from the two scanners over 30% and 60% peel regions at the 4% to 8% of distal tibia was analyzed. RESULTS: MDCT-based Tb measures characterizing bone network area density, plate-rod microarchitecture, and transverse trabeculae showed good correlations (r∈0.85,0.92) with the gold standard micro-CT-derived values of matching Tb measures. However, other MDCT-derived Tb measures characterizing trabecular thickness and separation, erosion index, and structure model index produced weak correlation (r<0.8) with their micro-CT-derived values. Most MDCT Tb measures were found repeatable (ICC∈0.94,0.98). The Tb plate-width measure showed a strong correlation (r = 0.89) with experimental yield stress, while the transverse trabecular measure produced the highest correlation (r = 0.81) with Young's modulus. The data continuity experiment showed that, despite significant differences in image resolution between two scanners (10% MTF along xy-plane and z-direction - Flash: 16.2 and 17.9 lp/cm; Force: 24.8 and 21.0 lp/cm), most Tb measures had high Pearson correlations (r > 0.95) between values estimated from the two scanners. Relatively lower correlation coefficients were observed for the bone network area density (r = 0.91) and Tb separation (r = 0.93) measures. CONCLUSION: Most MDCT-derived Tb microarchitectural measures are reproducible and their values derived from two scanners strongly correlate with each other as well as with bone strength. This study has highlighted those MDCT-derived measures which show the greatest promise for characterization of bone network area density, plate-rod and transverse trabecular distributions with a good correlation (r ≥ 0.85) compared with their micro-CT-derived values. At the same time, other measures representing trabecular thickness and separation, erosion index, and structure model index produced weak correlations (r < 0.8) with their micro-CT-derived values, failing to accurately portray the projected trabecular microarchitectural features. Strong correlations of Tb measures estimated from two scanners suggest that image data from different scanners can be used successfully in multisite and longitudinal studies with linear calibration required for some measures. In summary, modern MDCT scanners are suitable for effective quantitative imaging of peripheral Tb microarchitecture if care is taken to focus on appropriate quantitative metrics.

Impact of programs to reduce antipsychotic and anticholinergic use in nursing homes.

INTRODUCTION: Antipsychotics are used for managing behavioral and psychological symptoms of dementia (BPSD) but have risks. Anticholinergics can worsen outcomes in dementia. The Improving Antipsychotic Appropriateness in Dementia Patients educational program (IA-ADAPT) and Centers for Medicare and Medicaid Services Partnership to Improve Dementia Care (CMS Partnership) promote improved care for BPSD. The purpose of this study was to evaluate the impact of these programs on medication use and BPSD among nursing home residents. METHODS: This quasi-experimental longitudinal study used Medicare and assessment data for Iowa nursing home residents from April 2011 to December 2012. Residents were required to be eligible for six continuous months for inclusion. Antipsychotic use and anticholinergic use were evaluated on a monthly basis, and changes in BPSD were tracked using assessment data. Results are presented as odds ratios (ORs) per month after exposure to the IA-ADAPT or the start of the CMS Partnership. RESULTS: Of 426 eligible Iowa nursing homes, 114 were exposed to the IA-ADAPT in 2012. Nursing home exposure to the IA-ADAPT was associated with reduced antipsychotic use (OR [95% CI] = 0.92 [0.89-0.95]) and anticholinergic use (OR [95% CI] = 0.95 [0.92-0.98]), reduced use of excessive antipsychotic doses per CMS guidance (OR [95% CI] = 0.80 [0.75-0.86]), increased odds of a potentially appropriate indication among antipsychotic users (OR [95% CI] = 1.04 [1.00-1.09]), and decreased documentation of verbal aggression (OR [95% CI] = 0.96 [0.94-0.99]). Facilities with two or more IA-ADAPT exposures had greater reductions in antipsychotic and anticholinergic use than those with only one. The CMS Partnership was associated with reduced antipsychotic use (OR [95% CI] = 0.96 [0.94-0.98]) and decreased documentation of any measured BPSD (OR [95% CI] = 0.98 [0.97-0.99]) as well as delirium specifically (OR [95% CI] = 0.98 [0.96-0.99]). DISCUSSION: This study suggests that the IA-ADAPT and the CMS Partnership improved medication use with no adverse impact on BPSD.

Physical Activity, Not Sedentary Time, Predicts Dual-Energy X-ray Absorptiometry-measured Adiposity Age 5 to 19 Years.

PURPOSE: To examine the associations among physical activity (PA), sedentary time (SED), and TV viewing (TV) with fat mass (FAT) and visceral adipose tissue mass (VAT) from childhood through adolescence (5-19 yr). METHODS: Participants in the Iowa Bone Development Study (n = 230 males and 233 females) were examined at ages 5, 8, 11, 13, 15, 17, and 19 yr. Accelerometers measured moderate- or vigorous-intensity PA (MVPA; min·d), light-intensity PA (LPA; min·d), and SED (h·d). Parent-proxy report (5 and 8 yr) and child-report (11, 13, 15, 17, and 19 yr) measured TV (h·d). X-ray absorptiometry scans measured FAT (kg) and VAT (g). Sex-specific growth models were used to create FAT and VAT growth curves for individual participants (level 1), and to test the effect of MVPA, LPA, SED, and TV (level 2) after adjusting for weight, height, linear age, nonlinear age, and maturity. RESULTS: Growth models indicated that low levels of MVPA were associated with high levels of FAT and VAT for males and high levels of FAT for females. TV viewing was positively associated with FAT and VAT for males and females. LPA was positively associated with FAT in males. Sedentary time was not associated with FAT or VAT for males or females (P > 0.05). CONCLUSIONS: This study supports current PA guidelines focusing on MVPA rather than SED. The contribution of high TV, but not high SED, to high levels of adiposity suggests that TV's contribution to obesity is not just a function of low energy expenditure.

Association between body mass index percentile trajectories in infancy and adiposity in childhood and early adulthood.

OBJECTIVE: To identify distinct body mass index (BMI) percentile trajectories during early childhood and examine adiposity levels in childhood and early adulthood according to the BMI percentile trajectories. METHODS: Iowa Fluoride Study cohort parents (n = 1,093) reported their child's anthropometric data on average six times between ages 0 and 23 months. A subset of the cohort underwent DXA scans at approximately age 8 years (n = 495) and again at approximately age 19 years (n = 314). Group-based trajectory analysis was conducted to identify distinct BMI percentile trajectories from ages 0 to 23 months. Sex-specific age-adjusted linear regression analyses were conducted to compare fat mass index in childhood and early adulthood among subgroups that follow the distinct BMI percentile patterns. RESULTS: Four BMI percentile patterns were identified: consistently low (group 1: 9.8%), increase in the second year (group 2: 33.7%), increase in the first year (group 3: 23.9%), and consistently high (group 4: 32.6%). Compared with group 2 females, groups 3 and 4 females had higher fat mass index in childhood and early adulthood (P < 0.05). However, no significant difference was found in males. CONCLUSIONS: Females who experience a steep increase of BMI percentile in the first year of life, as opposed to a steep increase in the second year of life, may have higher body fat later in life, but this was not found in males.